Addiction neuroscience最新文献

This chapter covers how repetitive transcranial magnetic stimulation (rTMS) or transcranial direct current stimulation (tDCS) presently affects smoking cessation. 14 human studies have examined the efficacy of rTMS on cue craving, cigarette consumption, or smoking cessation using a variety of different coils, locations, and treatment parameters. These studies included 7 randomized-controlled trials (RCT) and 7 experimental studies. Most studies (12/14) reported that rTMS reduced cue-induced craving, 5 showed that it decreased cigarette consumption, and 3/4 reported that multiple sessions of rTMS increased the quit rate. In contrast to rTMS, tDCS has 6 RCT studies, of which only 2 studies reported that tDCS reduced craving, and only 1 reported that it reduced cigarette consumption. Three studies failed to find an effect of tDCS on cravings. No tDCS studies reported changing quitting rates in people who smoke. Despite the early positive results of tDCS on nicotine dependence symptoms, 2 larger RCTs recently failed to find a therapeutic effect of tDCS for smoking cessation. In conclusion, rTMS studies demonstrate that multiple sessions help quit smoking, and it has gained FDA approval for that purpose. However, more studies are needed to examine the effect of tDCS with different treatment parameters.

Cigarette smoking has been associated with epigenetic alterations that may be reversible upon cessation. As the most-studied epigenetic modification, DNA methylation is strongly associated with smoking exposure, providing a potential mechanism that links smoking to adverse health outcomes. Here, we reviewed the reversibility of DNA methylation in accessible peripheral tissues, mainly blood, in relation to cigarette smoking cessation and the utility of DNA methylation as a biomarker signature to differentiate current, former, and never smokers and to quantify time since cessation. We summarized thousands of differentially methylated Cytosine-Guanine (CpG) dinucleotides and regions associated with smoking cessation from candidate gene and epigenome-wide association studies, as well as the prediction accuracy of the multi-CpG predictors for smoking status. Overall, there is robust evidence for DNA methylation signature of cigarette smoking cessation. However, there are still gaps to fill, including (1) cell-type heterogeneity in measuring blood DNA methylation; (2) underrepresentation of non-European ancestry populations; (3) limited longitudinal data to quantitatively measure DNA methylation after smoking cessation over time; and (4) limited data to study the impact of smoking cessation on other epigenetic features, noncoding RNAs, and histone modifications. Epigenetic machinery provides promising biomarkers that can improve success in smoking cessation in the clinical setting. To achieve this goal, larger and more-diverse samples with longitudinal measures of a broader spectrum of epigenetic marks will be essential to developing a robust DNA methylation biomarker assay, followed by meeting validation requirements for the assay before being implemented as a clinically useful tool.

Objective

Stressors are associated with greater alcohol consumption, alcohol-related problems, and Alcohol Use Disorder. Implicit cognitive processes are key in determining a coping strategy but alcohol and stressors may interfere with these processes. One such process, alcohol attention bias (AtB), has been associated with hazardous and coping-motivated alcohol use patterns. This study 1) tested associations between alcohol AtB, hazardous alcohol use patterns, and coping motivation and 2) tested alcohol AtB as a mediator in the stressor-alcohol relationship.

Method

Thirty-nine participants with hazardous alcohol use were randomly assigned to a stress-exposure or control condition. Participants completed assessments of alcohol use patterns, coping motivation, stress response, alcohol craving, and alcohol AtB. Outcome measures were alcohol craving and consumption. Bivariate associations, ANCOVAs, and serial mediation models were used to test hypotheses.

Results

Significant associations were found between alcohol AtB, hazardous alcohol use pattern, and coping motivation. Analyses revealed no significant differences in alcohol outcomes and no significant serial mediation effect.

Conclusions

Bivariate associations were consistent with previous research. Lack of power to detect significant effects due to small sample size may explain null serial mediation results. Alternative explanations include measurement of alcohol AtB and stress response, which highlight important considerations for future research.

This review summarizes the evidence to date on the development of biomarkers for personalizing the pharmacological treatment of combustible tobacco use. First, the latest evidence on FDA-approved medications is considered, demonstrating that, while these medications offer real benefits, they do not contribute to smoking cessation in approximately two-thirds of cases. Second, the case for using biomarkers to guide tobacco treatment is made based on the potential to increase medication effectiveness and uptake and reduce side effects. Next, the FDA framework of biomarker development is presented along with the state of science on biomarkers for tobacco treatment, including a review of the nicotine metabolite ratio, electroencephalographic event-related potentials, and other biomarkers utilized for risk feedback. We conclude with a discussion of the challenges and opportunities for the translation of biomarkers to guide tobacco treatment and propose priorities for future research.

This systematic review aims to characterize the utility of machine learning to identify the predictors of smoking cessation outcomes and identify the machine learning methods applied in this area. In the current study, multiple searches occurred through December 9, 2022 in MEDLINE, Science Citation Index, Social Science Citation Index, EMBASE, CINAHL Plus, APA PsycINFO, PubMed, Cochrane Central Register of Controlled Trials, and the IEEE Xplore were performed. Inclusion criteria included various machine learning techniques, studies reporting cigarette smoking cessation outcomes (smoking status and the number of cigarettes), and various experimental designs (e.g., cross-sectional and longitudinal). Predictors of smoking cessation outcomes were assessed, including behavioral markers, biomarkers, and other predictors. Our systematic review identified 12 papers fitting our inclusion criteria. In this review, we identified gaps in knowledge and innovation opportunities for machine learning research in the field of smoking cessation.

Cigarette smoking remains as a major preventable cause of morbidity and mortality around the world. Smoking causes many diseases and use of tobacco products is known to have detrimental effects on the user, leading to the causation of numerous adverse health outcomes.

Evaluation of the user's risk following cessation of tobacco products has shown to vary with the affected organ, reflecting the temporal dynamics of the underlying disease processes. The potential utility of biomarkers for smoking cessation can provide a measure of the damage from use of tobacco products and the impact on affected organs after cessation of tobacco products.

For this review we focus on three common sets of diseases for which there are potential biomarkers of improved health within a relatively short period of time after smoking cessation: cardiovascular disease (CVD), chronic obstructive pulmonary disease (COPD), and oral disease. For each set of diseases, we provide an overview including disease burden and epidemiology; a discussion of disease process/pathogenesis; potential biomarkers of improved health after smoking cessation with examples of their application; and future directions.

Globally, methamphetamine is one of the most widely used illicit substances. Despite this, there are no Food and Drug Administration (FDA)-approved pharmacotherapies for treating methamphetamine use disorder. Accumulating evidence suggests consistent cognitive impairments in people with methamphetamine use disorder, which are also associated with neural dysfunction. Importantly, improving cognition may be highly beneficial in reducing methamphetamine use. Indeed, there are medications that have been or are currently being assessed in clinical trials as repurposing drugs to treat methamphetamine use disorder and associated cognitive deficits. Given the known safety profiles and bioavailability, as well as established manufacturing processes, drug repurposing can bypass some steps of conventional drug discovery. This shortens the timeline from bench to bedside translation with lower cost and less risk. Hence, drug repurposing to find pharmacotherapies to treat methamphetamine use disorder should be highly encouraged. The aim of the present review is to scope all repurposed medications in past and current clinical trials in people with methamphetamine use disorder that also assess cognitive function. Medications were selected from publicly available clinical trials registration databases. Based on human and animal literature, we will describe their putative mechanism of action, pharmacological properties, and their potential to improve cognitive functioning in people who use methamphetamine. We hope this scoping review will stimulate drug repurposing and promote rigorous neuroscience-based rationale in future clinical trials to treat methamphetamine use disorder.

Drug associated cues are a common relapse trigger for individuals recovering from cocaine use disorder. Sex and ovarian hormones influence patterns of cocaine use and relapse vulnerability, with studies indicating that females show increased cue-induced craving and relapse vulnerability compared to males. In a rodent model of cocaine craving and relapse vulnerability, cue-induced cocaine seeking behavior following weeks of withdrawal from extended-access cocaine self-administration is higher in females in the estrus stage of the reproductive (estrous) cycle (Estrus Females) compared to both Males and females in all other stages (Non-Estrus Females). However, the neuronal substrates and cellular mechanisms underlying these sex differences is not fully understood. One region that contributes to both sex differences in behavioral responding and cue-induced cocaine seeking is the basolateral amygdala (BLA), while one receptor known to play a critical role in mediating cocaine seeking behavior is metabotropic glutamate receptor 5 (mGlu5). Here we assessed the effects of BLA mGlu5 inhibition following prolonged withdrawal from cocaine self-administration on observed estrous cycle-dependent changes in cue-induced cocaine seeking behavior. We found that BLA microinjections of the mGlu5 antagonist MTEP selectively reduced the enhanced cue-induced cocaine seeking normally observed in Estrus Females while having no effect on cocaine seeking in Males and Non-Estrus Females. These findings identify a unique interaction between cocaine-exposure, estrous cycle fluctuations and BLA mGlu5-dependent transmission on cue-induced cocaine seeking behavior.

Substance use disorder (SUD) is characterized, in part, by lack of control over drug seeking and taking. The prefrontal cortex (PFC) is highly involved in control of behavior and deficits in PFC structure and function have been demonstrated in clinical and preclinical studies of SUD. Of the various classes of drugs associated with the development of SUD, inhalants are among the least studied despite their widespread use among adolescents and children. In this work, we review what is currently known regarding the sites and mechanisms of action of inhalants with a focus on the volatile solvent toluene that is contained in a wide variety of legal and easily obtained products. We then describe how inhalants including toluene affect various behaviors with an emphasis on those associated with PFC function and how chronic use of inhalants alters brain structure and neuronal signaling. Findings from these studies highlight advances made in recent years that have expanded our understanding of the effects of inhalants on brain structure and reinforce the need for continued work in this field.